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Title: Mechanisms underlying the attenuation of the neuroendocrine response of the hypothalamic-pituitary-adrenal axis to acute stress in the late pregnant rat
Author: Johnstone, Heather A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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The aim of this PhD project was to examine whether HPA axis responses to acute stress were different during pregnancy and to elucidate possible mechanisms underlying these changes. We found that on day 21 of pregnancy the peak plasma adrenocorticotrophic hormone (ACTH) and corticosterone secretory responses to 20 min of restraint stress were significantly reduced. Using receptor autoradiography we found that between day 10 and day 21 of pregnancy there was a progressive decrease in the binding of corticotropin-releasing factor (CRF) to anterior pituitary sections. When we examined the responsiveness of the anterior pituitary in vitro, by exposing both pituitary segments and acutely dispersed anterior pituitary cells to CRF and measuring the accumulation of cAMP, we found that on day 21 of pregnancy the anterior pituitary was less responsive. Using in situ hybridisation histochemistry to investigate the basal expression of CRF and arginine vasopressin (AVP) genes to the parvocellular paraventricular nucleus (PVN), we demonstrated that on day 21 of pregnancy there was a significant reduction in CRF, but not AVP mRNA. We examined whether there was an increase in the sensitivity of the HPA axis to the glucocorticoid negative feedback signal. Using in situ hybridisation histochemistry we measured the basal expression of the mRNAs for mineralocorticoid (MR) and glucocorticoid (GR) receptors in the PVN and hippocampus and found that neither mRNA was altered during pregnancy. We also measured in vitro the bioactivity of the glucocorticoid-metabolising enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in PVN, anterior pituitary and hippocampus and found that the enzyme activity increased almost 3-fold selectively in the PVN on day 21 of pregnancy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available